Joris R. de Groot

Sudden Cardiac Death in Adult Congenital Heart Disease

Background— Sudden cardiac death (SCD) is a major cause of mortality in adults with congenital heart disease (CHD). The aim of this study was to determine the adult CHD population at risk of SCD and the clinical parameters associated with SCD. Methods and Results— We performed a multicenter case-control study. Patients who died suddenly as a result of proven or presumed arrhythmia were included (cases). For each case, 2 controls matched on diagnosis, type of surgical intervention, age, and gender were included. From 3 databases including 25 790 adults with CHD, 1189 deaths (5%) were identified, of whom 213 patients (19%) died suddenly. Arrhythmic death occurred in 171 of 1189 patients. The underlying cardiac lesions were mild, moderate, and severe CHD in 12%, 33%, and 55% of the SCD cases, respectively. Clinical variables associated with SCD were supraventricular tachycardia (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.5–7.9; P=0.004), moderate to severe systemic ventricular dysfunction (OR, 3.4; 95% CI, 1.1–10.4; P=0.034), moderate to severe subpulmonary ventricular dysfunction (OR, 3.4; 95% CI, 1.1–10.2; P=0.030), increased QRS duration (OR, 1.34 [per 10-ms increase]; 95% CI, 1.10–1.34; P=0.008), and QT dispersion (OR, 1.22 [per 10-ms increase]; 95% CI, 1.22–1.48; P=0.008). Conclusions— The clinical parameters found to be associated with SCD in adults with a broad spectrum of CHD, including systemic right ventricles, are similar to those in ischemic heart disease. Moreover, even those patients with mild cardiac lesions are potentially at risk for SCD. This highlights the need for further prospective studies as well as vigilant ongoing follow-up of the adult with CHD.

The entirely subcutaneous implantable cardioverter-defibrillator: initial clinical experience in a large Dutch cohort.

OBJECTIVES The purpose of the study was to evaluate the efficacy and safety of the entirely subcutaneous implantable cardioverter-defibrillator (S-ICD). BACKGROUND A new entirely S-ICD has been introduced, that does not require lead placement in or on the heart. The authors report the largest multicenter experience to date with the S-ICD with a minimum of 1-year follow-up in the first 118 Dutch patients who were implanted with this device. METHODS Patients were selected if they had a class I or IIa indication for primary or secondary prevention of sudden cardiac death. All consecutive patients from 4 high-volume centers in the Netherlands with an S-ICD implanted between December 2008 and April 2011 were included. RESULTS A total of 118 patients (75% males, mean age 50 years) received the S-ICD. After 18 months of follow-up, 8 patients experienced 45 successful appropriate shocks (98% first shock conversion efficacy). No sudden deaths occurred. Fifteen patients (13%) received inappropriate shocks, mainly due to T-wave oversensing, which was mostly solved by a software upgrade and changing the sensing vector of the S-ICD. Sixteen patients (14%) experienced complications. Adverse events were more frequent in the first 15 implantations per center compared with subsequent implantations (inappropriate shocks 19% vs. 6.7%, p = 0.03; complications 17% vs. 10%, p = 0.10). CONCLUSIONS This study demonstrates that the S-ICD is effective in terminating ventricular arrhythmias. There is, however, a considerable percentage of ICD related adverse events, which decreases as the therapy evolves and experience increases.

Thoracoscopic Video-Assisted Pulmonary Vein Antrum Isolation, Ganglionated Plexus Ablation and Periprocedural Confirmation of Ablation Lesions. First Results of a Hybrid Surgical-Electrophysiological Approach for Atrial Fibrillation

Background—Thoracoscopic pulmonary vein isolation (PVI) and ganglionated plexus ablation is a novel approach in the treatment of atrial fibrillation (AF). We hypothesize that meticulous electrophysiological confirmation of PVI results in fewer recurrences of AF during follow-up. Methods and Results—Surgery was performed through 3 ports bilaterally. Ganglionated plexi were localized and subsequently ablated. PVI was performed and entry and exit block was confirmed. Additional left atrial ablation lines were created and conduction block verified in patients with nonparoxysmal AF. The left atrial appendage was removed. Freedom of AF was assessed by ECGs and Holter monitoring every 3 months or during symptoms of arrhythmia. Antiarrhythmic drugs were discontinued after 3 months and oral anticoagulants were discontinued according to the guidelines. Thirty-one patients were treated (16 paroxysmal AF, 13 persistent AF, 2 long-standing persistent AF). Thirteen patients with nonparoxysmal received additional left atrial ablation lines. After 1 year, 19 of 22 patients (86%) had no recurrences of AF, atrial flutter, or atrial tachycardia and were not using antiarrhythmic drugs (11/12 paroxysmal, 7/9 persistent, and 1/1 long-standing persistent). Three patients had a sternotomy because of uncontrolled bleeding during thoracoscopic surgery. Four adverse events were 1 hemothorax, 1 pneumothorax, and 2 pneumonia. No thromboembolic complications or mortality occurred. Conclusions—Thoracoscopic surgery with PVI and ganglionated plexus ablation for AF is a safe and successful procedure with a single procedure success rate of 86% at 1 year. Electrophysiological guided thorough PVI and additional left atrial ablation line creation presumably contributes in achieving a high success rate in the surgical treatment of AF.

Permanent Leadless Cardiac Pacing: Results of the LEADLESS Trial

Background— Conventional cardiac pacemakers are associated with several potential short- and long-term complications related to either the transvenous lead or subcutaneous pulse generator. We tested the safety and clinical performance of a novel, completely self-contained leadless cardiac pacemaker. Methods and Results— The primary safety end point was freedom from complications at 90 days. Secondary performance end points included implant success rate, implant time, and measures of device performance (pacing/sensing thresholds and rate-responsive performance). The mean age of the patient cohort (n=33) was 77±8 years, and 67% of the patients were male (n=22/33). The most common indication for cardiac pacing was permanent atrial fibrillation with atrioventricular block (n=22, 67%). The implant success rate was 97% (n=32). Five patients (15%) required the use of >1 leadless cardiac pacemaker during the procedure. One patient developed right ventricular perforation and cardiac tamponade during the implant procedure, and eventually died as the result of a stroke. The overall complication-free rate was 94% (31/33). After 3 months of follow-up, the measures of pacing performance (sensing, impedance, and pacing threshold) either improved or were stable within the accepted range. Conclusions— In a prospective nonrandomized study, a completely self-contained, single-chamber leadless cardiac pacemaker has shown to be safe and feasible. The absence of a transvenous lead and subcutaneous pulse generator could represent a paradigm shift in cardiac pacing. Clinical Trial Registration— URL: . Unique identifier: [NCT01700244][1]. # CLINICAL PERSPECTIVE {#article-title-26} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01700244&atom=%2Fcirculationaha%2F129%2F14%2F1466.atomBackground— Conventional cardiac pacemakers are associated with several potential short- and long-term complications related to either the transvenous lead or subcutaneous pulse generator. We tested the safety and clinical performance of a novel, completely self-contained leadless cardiac pacemaker. Methods and Results— The primary safety end point was freedom from complications at 90 days. Secondary performance end points included implant success rate, implant time, and measures of device performance (pacing/sensing thresholds and rate-responsive performance). The mean age of the patient cohort (n=33) was 77±8 years, and 67% of the patients were male (n=22/33). The most common indication for cardiac pacing was permanent atrial fibrillation with atrioventricular block (n=22, 67%). The implant success rate was 97% (n=32). Five patients (15%) required the use of >1 leadless cardiac pacemaker during the procedure. One patient developed right ventricular perforation and cardiac tamponade during the implant procedure, and eventually died as the result of a stroke. The overall complication-free rate was 94% (31/33). After 3 months of follow-up, the measures of pacing performance (sensing, impedance, and pacing threshold) either improved or were stable within the accepted range. Conclusions— In a prospective nonrandomized study, a completely self-contained, single-chamber leadless cardiac pacemaker has shown to be safe and feasible. The absence of a transvenous lead and subcutaneous pulse generator could represent a paradigm shift in cardiac pacing. Clinical Trial Registration— URL: http://clinicaltrials.gov. Unique identifier: NCT01700244.

Rationale and design of the PRAETORIAN trial: A Prospective, RAndomizEd comparison of subcuTaneOus and tRansvenous ImplANtable cardioverter-defibrillator therapy

BACKGROUND Implantable cardioverter-defibrillators (ICDs) are widely used to prevent fatal outcomes associated with life-threatening arrhythmic episodes in a variety of cardiac diseases. These ICDs rely on transvenous leads for cardiac sensing and defibrillation. A new entirely subcutaneous ICD overcomes problems associated with transvenous leads. However, the role of the subcutaneous ICD as an adjunctive or primary therapy in patients at risk for sudden cardiac death is unclear. STUDY DESIGN The PRAETORIAN trial is an investigator-initiated, randomized, controlled, multicenter, prospective 2-arm trial that outlines the advantages and disadvantages of the subcutaneous ICD. Patients with a class I or IIa indication for ICD therapy without an indication for bradypacing or tachypacing are included. A total of 700 patients are randomized to either the subcutaneous or transvenous ICD (1:1). The study is powered to claim noninferiority of the subcutaneous ICD with respect to the composite primary endpoint of inappropriate shocks and ICD-related complications. After noninferiority is established, statistical analysis is done for potential superiority. Secondary endpoint comparisons of shock efficacy and patient mortality are also made. CONCLUSION The PRAETORIAN trial is a randomized trial that aims to gain scientific evidence for the use of the subcutaneous ICD compared with the transvenous ICD in a population of patients with conventional ICD with respect to major ICD-related adverse events. This trial is registered at ClinicalTrials.gov with trial ID NCT01296022.

The ICD for Primary Prevention in Patients With Inherited Cardiac Diseases Indications, Use, and Outcome: A Comparison With Secondary Prevention

Background— Indications for prophylactic implantable cardioverter-defibrillator (ICD) therapy in patients with inherited cardiac diseases stem from observational studies and are uncertain. This study evaluates the efficacy and harm rate of ICD implantations for primary prevention compared with secondary prevention in inherited cardiac diseases. Methods and Results— Between January 1, 1993, and April 1, 2011, 354 patients with inherited cardiac diseases were treated with ICDs. Incidence rates of appropriate shocks in primary prevention patients with arrhythmogenic right ventricular cardiomyopathy and hypertrophic cardiomyopathy were 4.2 to 6.7/100 patient-years, whereas the risk for appropriate shocks in primary prevention patients with Brugada syndrome, long QT syndrome, or carrying the DPP6 haplotype approached zero. Conversely, in secondary prevention patients there was a considerably higher incidence rate of appropriate shocks. None of the indications for primary prevention were associated with appropriate shock therapy. One hundred twenty-three patients (35%) experienced ICD-related adverse events. Conclusions— For Brugada syndrome, long QT syndrome, and DPP6 the efficacy of an ICD for primary prevention contrasts with the amount of harm, and factors that formed the indication for ICD implantation do not relate to the occurrence of appropriate shocks. The higher appropriate discharge rates in arrhythmogenic right ventricular cardiomyopathy and hypertrophic cardiomyopathy compared with primary electric diseases might result from a more advanced risk stratification scheme in these inherited cardiomyopathies.Background—Indications for prophylactic implantable cardioverter-defibrillator (ICD) therapy in patients with inherited cardiac diseases stem from observational studies and are uncertain. This study evaluates the efficacy and harm rate of ICD implantations for primary prevention compared with secondary prevention in inherited cardiac diseases. Methods and Results—Between January 1, 1993, and April 1, 2011, 354 patients with inherited cardiac diseases were treated with ICDs. Incidence rates of appropriate shocks in primary prevention patients with arrhythmogenic right ventricular cardiomyopathy and hypertrophic cardiomyopathy were 4.2 to 6.7/100 patient-years, whereas the risk for appropriate shocks in primary prevention patients with Brugada syndrome, long QT syndrome, or carrying the DPP6 haplotype approached zero. Conversely, in secondary prevention patients there was a considerably higher incidence rate of appropriate shocks. None of the indications for primary prevention were associated with appropriate shock therapy. One hundred twenty-three patients (35%) experienced ICD-related adverse events. Conclusions—For Brugada syndrome, long QT syndrome, and DPP6 the efficacy of an ICD for primary prevention contrasts with the amount of harm, and factors that formed the indication for ICD implantation do not relate to the occurrence of appropriate shocks. The higher appropriate discharge rates in arrhythmogenic right ventricular cardiomyopathy and hypertrophic cardiomyopathy compared with primary electric diseases might result from a more advanced risk stratification scheme in these inherited cardiomyopathies.

Implantable cardioverter defibrillator therapy in adults with congenital heart disease: who is at risk of shocks?

Background— The value of implantable cardioverter defibrillators (ICDs) in adults with congenital heart disease (CHD) is unknown. We investigated the long-term outcome after ICD implantation and developed a simple risk stratification score for ICD therapy. Methods and Results— A total of 136 adults with CHD and ICD (mean age±SD, 41±13 years; 67% male) were identified from 10 tertiary referral centers in the Netherlands and Belgium. The indication for ICD implantation was primary prevention in 50% of patients. Diagnoses included tetralogy of Fallot (51%), septal defects (20%), (congenitally corrected) transposition of the great arteries (13%), and other (16%). Thirty-nine patients (29%) received appropriate ICD shocks during a median follow-up of 4.6 years. Secondary prevention indication (hazard ratio [HR], 3.6; 95% CI, 1.3–9.5; P=0.009), coronary artery disease (HR, 2.7; 95% CI, 1.0–7.2; P=0.042), and symptomatic nonsustained ventricular tachycardia (NSVT; HR, 9.1; 95% CI, 2.8–29.2; P=0.001) were associated with appropriate ICD shocks. A risk score was developed to evaluate the likelihood of appropriate ICD shocks. The 8-year survival curve to first appropriate shocks was 94%, 57%, and 26% for low-, intermediate-, and high-risk patients, respectively. In primary prevention, symptomatic NSVTs (HR, 8.0; 95% CI, 2.3–27.1; P=0.001) and subpulmonary ventricular dysfunction (HR, 3.0; 95% CI, 1.2–12.6; P=0.02) were associated with appropriate shocks in univariable analysis. Inappropriate shocks occurred in 41 patients (30%). In addition, 40 patients (29%) experienced 45 implantation-related complications. Conclusions— Adults with CHD and ICDs receive high rates of appropriate and effective shocks. Patients with secondary prevention indication, coronary artery disease, and symptomatic NSVT are at highest risk of receiving appropriate ICD shocks. ICD implantation is accompanied by considerable morbidity, including inappropriate shocks and procedure- related complications.

Navigating the mini-maze: Systematic review of the first results and progress of minimally-invasive surgery in the treatment of atrial fibrillation

BACKGROUND In this paper we present a systematic literature overview and analysis of the first results and progress made with minimally-invasive surgery using RF energy in the treatment of AF. The minimally-invasive treatment for atrial fibrillation (AF) tries to combine the success rate of surgical treatment with a less invasive approach to surgery. It has the additional potential advantage of ganglion plexus (GP) ablation and left atrial appendage exclusion. Furthermore, additional left atrial ablation lines (ALAL) can be created in non-paroxysmal AF patients. METHODS For the search query multiple databases were used. Exclusion and inclusion criteria were applied to select the publications to be screened. All remaining articles were critically appraised and only relevant and valid articles were included in our results. RESULTS Twenty-three studies were included. In 15 studies GPs around the pulmonary veins were ablated. In four studies ALAL were performed. Single procedure success rate was 69% (95% CI, range 58%-78%) without antiarrhythmic drugs (AAD) and 79% (95% CI, range 71%-85%) with AAD at one year follow-up. Mortality was 0.4%, and various complications were reported (3.2% surgical, 3.2% post-surgical, 2.6% cardiac, 2.1% pulmonary, 1.7% other). CONCLUSIONS Twenty-three studies of minimally-invasive surgery for AF have been reviewed with success rates between that of the standard maze procedure and catheter ablation. These first combined results show promise; however, minimally-invasive surgery is still evolving, for instance by the recent inclusion of electrophysiological endpoints. Furthermore, the type of ALAL and the additional value of GP ablation have to be elucidated.

Right ventricular pacing improves haemodynamics in right ventricular failure from pressure overload: an open observational proof-of-principle study in patients with chronic thromboembolic pulmonary hypertension

AIMS Right ventricular (RV) failure in patients with chronic thromboembolic pulmonary hypertension (CTEPH), and other types of pulmonary arterial hypertension is associated with right-to-left ventricle (LV) delay in peak myocardial shortening and, consequently, the onset of diastolic relaxation. We aimed to establish whether RV pacing may resynchronize the onsets of RV and LV diastolic relaxation, and improve haemodynamics. METHODS AND RESULTS Fourteen CTEPH patients (mean age 63.7 ± 12.0 years, 10 women) with large (≥60 ms) RV-to-LV delay in the onset of diastolic relaxation (DIVD, diastolic interventricular delay) were studied. Temporary RV pacing was performed by atrioventricular (A-V) sequential pacing with incremental shortening of A-V delay to advance RV activation. Effects were assessed using tissue Doppler echocardiography and LV pressure-conductance catheter measurements in a subset of patients. Compared with right atrial pacing, RV pacing at optimal A-V delay (average 140 ± 22 ms, range 120-180 ms) resulted in significant DIVD reduction (59 ± 19 to 3 ± 22 ms, P < 0.001), and increase in LV stroke volume as measured by LV outflow tract velocity-time integral (14.9 ± 2.8 to 16.9 ± 3.0 cm, P < 0.001), along with enhanced global RV contractility and LV diastolic filling. CONCLUSION Right-to-left ventricle resynchronization of the onset of diastolic relaxation results in stroke volume increase in CTEPH patients. Whether RV pacing may be a novel therapeutic target in RV failure following chronic pressure overload remains to be investigated.

Interactions between antiarrhythmic drugs and cardiac memory.

OBJECTIVE Ventricular pacing or arrhythmias can induce cardiac memory (CM). We hypothesized that clinically administered antiarrhythmic drugs alter the expression of CM, and that the repolarization changes characteristic of CM can modulate the effects of antiarrhythmic drugs. METHODS We studied conscious, chronically-instrumented dogs paced for two 1-h periods to study the effects of drugs on the evolution of memory (protocol 1) or for 21 days (protocol 2) to observe the effects of steady-state memory on drug actions. Dogs were treated in both settings with quinidine, lidocaine or E4031, in random order, and within therapeutic serum concentration ranges. RESULTS Pacing, alone, for 2 h significantly prolonged ERP only near the left ventricular pacing site, whereas pacing alone for 21 days prolonged ERP at all sites (P<0.05). Quinidine and E4031, but not lidocaine, prolonged repolarization and ERP and suppressed evolution of CM in protocol 1. However, quinidines effect in prolonging repolarization was diminished in both protocols, while its effect in prolonging ERP was diminished in the 21-day protocol only. In contrast, the effects of E4031 were additive to those of CM, prolonging repolarization and ERP in both protocols, while lidocaine showed no changes in effect at all. CONCLUSIONS Pacing to induce CM significantly affects ventricular repolarization and refractoriness, and there are interactions between CM, quinidine and E4031. Depending on the specific drug, these interactions have the potential to be anti- or proarrhythmic, and may impact importantly on the clinical efficacy of drugs as well as on electrophysiologic testing of drug actions.